This proposal aims to establish a new In Vivo Cellular and Molecular Imaging Center at Vanderbilt University which will be dedicated to providing the scientific and technical resources to develop, support and integrate highly innovative molecular imaging studies of cancer biology of direct relevance and translational potential to clinical cancer care. The proposed center will bring together an outstanding team of investigators from diverse disciplines, including leaders in imaging science, clinical oncology, the design and development of molecular probes, and cancer biology. The ICMIC will be housed in a leading medical center which is widely recognized for its highly collegia! and interactive environment, and which emphasizes the importance of multidisciplinary approaches to medical research. The mission of the proposed ICMIC will be to develop and apply novel imaging biomarkers for the non-invasive, quantitative assessment of the molecular and cellular mechanisms of response to targeted treatment of tumors in vivo. The ICMIC will establish four Specialized Resources: a Small Animal Imaging Core;a Chemistry Core;a Radiochemistry Core;and a Biostatistics Core. These resources will support programs focused on the development and application of sensitive new imaging probes and methods for assessing how specific molecular signal transduction pathways, and the physiological sequelae to changes in these pathways, are modified by cancer and cancer therapy. The ICMIC will support 4 related major Projects. [1] Molecular Imaging to Evaluate EGFR and SRCtrageted therapies in Colorectal Cancer [2] Imaging Tumor Expression of Cyclooxygenase-2 [3] Noninvasive Assessment of Cancer Responsiveness to Therapy by use of Recombinant Peptide Ligands and [4] Proteolytic Beacons in the Non-invasive Assessment of Response to Cancer Therapy. All four projects will quantitatively and longitudinally assess the response mechanisms of novel, targeted anti-cancer treatments using novel, targeted imaging probes (via optical, PET, and SPECT) which will be complemented by measuring downstream physiological effects (via ultrasound, MRI, and CT). There will be synergy between the cores and the projects, which share common concepts of developing quantitative biomarkers of the effects of therapies that target specific cell signal transduction pathways. The ICMIC will also support new research directions via Discovery Grants for Pilot Projects, and undertake a program of Career Development to nurture scientists and physicians to become independent investigators in molecular imaging of cancer. The infrastructure and resources of the ICMIC will be provided by the Vanderbilt University Institute of Imaging Science, a key resource and program of the Vanderbilt-lngram Cancer Center, a leading comprehensive cancer center. The ICMIC will build upon existing programs, resources and institutional commitments to create an exemplary environment for research and training in molecular imaging.